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Protein Metabolism(II)
Dr Bushra Ahmed
1
Learning Objectives
By the end of this session and with some further study you
should be able to explain:
Fate of the Carbon Skeletons of Deaminated amino acids
Errors in amino acid catabolism
The urea cycle disorder
Breakdown of Carbon Skeletons Involves
Complex Reaction Pathways
Lys
4 steps
Trp
9 steps
α-Ketoadipate
Ala
Pyruvate
Glutaryl-CoA
4 steps
Acetoacetyl-CoA
Acetyl-CoA
3
Fate of the Carbon Skeletons of Deaminated
Amino Acids
Amino acids are classified as glucogenic or
ketogenic
...
The NH3 and HCO3− (carbonyl C) that will be part of
urea are incorporated first into carbamoyl
phosphate
...
An ornithine/citrulline transporter in the inner
mitochondrial membrane facilitates transmembrane fluxes of
citrulline & ornithine
...
Oxaloacetate is converted to aspartate via
transamination (e
...
, from glutamate)
...
COO−
COO−
COO−
CH2
COO−
CH2
CH2
CH2
CH2
CH2
HC
NH3+
COO−
+
C
O
COO−
C
O
COO−
+
HC
NH3+
COO−
aspartate α-ketoglutarate oxaloacetate glutamate
Aminotransferase (Transaminase)
14
cytosol
mitochondrial matrix
Mainly the process
of Urea Cycle occurs
in the Liver
However arginine &
ornithine are
generated in other
tissues
carbamoyl phosphate
Pi
ornithine
citrulline
ornithine
citrulline
aspartate
argininosuccinate
urea
arginine
fumarate
E
...
, Argininosuccinate Synthase, which
catalyzes synthesis of the precursor to arginine, is present in
most tissues
...
15
Carbamoyl Phosphate
Synthase (Type I)
catalyzes a 3-step
reaction, with carbonyl
phosphate and
carbamate
intermediates
HCO3− + NH3 + 2 ATP
O
H2N
C
Carbamoyl Phosphate
Synthase
OPO32− + 2 ADP + Pi
carbamoyl phosphate
16
NH2
C
+
NH2
NH
C
NADPH
NADP+
CH2
O2
CH
C
OH
CH2
O2
arginine
+
H3 N
CH
+
NO
CH2
H2O
CH2
CH2
COO−
O
NH
1/2 NADPH 1/2 NADP+
CH2
H2O
CH2
H3N
NH
N
CH2
CH2
+
NH2
NH2
COO−
hydroxyarginine
+
H3N
CH
COO−
citrulline
Nitric Oxide Synthase
Arginine is an essential part of proteins, & is precursor for
synthesis of creatine and nitric oxide (·NO)
...
It plays several roles in
different cell types:
regulating smooth muscle contraction, gene transcription,
metabolism, & neurotransmission